New compositions and methods for the treatment of inflammation

A method of treating an inflammatory disorder, comprising administering to a subject suffering from the disorder, a composition comprising:

• a) an effective amount of at least one adenosine A2A receptor agonist and
• b) an effective amount of at least one anti-inflammatory compound, wherein the anti-inflammatory compound is other than a PDE4 inhibitor and the adenosine A2A receptor agonist is of formula (I):
• wherein:
• X1 is selected from —OR1, —NR2R3, —C≡C—Z, and —NH—N═R4;
• R1 is selected from:
• (a) C1-4 alkyl;
• (b) C1-4 alkyl substituted with one or more C1-4 alkoxy, halogen, hydroxy, amino, mono(C1-4 alkyl)amino, di(C1-4 alkyl)amino, and C6-10 aryl, wherein aryl may be substituted with one or more halogen, C1-4 alkyl, hydroxy, amino, mono(C1-4 alkyl)amino, di(C1-4 alkyl)amino, and R15OOC—C1-4 alkyl-;
• (c) C6-10 aryl;
• and
• (d) C6-10 aryl substituted with one or more halogen, hydroxy, amino, mono(C1-4 alkyl)amino, di(C1-4 alkyl)amino, and C1-4 alkyl;
• one of R2 and R3 has the same meaning as R1 and the other is hydrogen;
• R4 is a group having the formula:
• R5 and R6 are independently selected from H, C3-7-cycloalkyl, or any of the meanings of R1, provided that R5 and R6 are not both hydrogen;
• Z is selected from (a)-(e):
• a) phenyl or naphthyl optionally substituted with one to three groups selected from halogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C2-6 alkoxycarbonyl, C2-6 alkoxyalkyl, C1-6 alkylthio, thio, CHO, cyanomethyl, nitro, cyano, hydroxy, carboxy, C2-6 acyl, amino, C1-3 monoalkylamino, C2-6 dialkylamino, methylenedioxy;
• and aminocarbonyl;
• b) a group of formula —(CH2)m-Het, wherein m is 0 or an integer from 1 to 3 and Het is 5-6 membered heterocyclic aromatic or non-aromatic ring, optionally benzo condensed, containing 1-3 heteroatoms selected from nonperoxide oxygen, nitrogen, and sulfur, linked through a carbon atom or through a nitrogen atom;
• c) C2-C4 alkenyl or C3-C7 cycloalkyl optionally containing unsaturation;
• d)
• and,
• e) C1-C16 alkyl, optionally comprising 1-2 double bonds, O, S or NY;
• R10 is selected from H, methyl, and phenyl;
• R12 is selected from H, C1-C6 alkyl, C5-C6 cycloalkyl, C3-C7 cycloalkenyl, and phenyl-C1-2 alkyl-;
• alternatively, R10 and R12, taken together, form a 5- or 6-membered carbocyclic ring;
• alternatively, R3 is hydrogen and R2 and R4, taken together, form an oxo group or a corresponding acetalic derivative;
• R11 is selected from OH, NH2 dialkylamino, halogen, and cyano;
• n is selected from 0, 1, 2, 3, and;
• Y is individually selected from H, C1-6 alkyl, C3-7 cycloalkyl, phenyl, and phenyl-C1-3 alkyl-;
• R20 is selected from —C(═O)NR16R17, —COOR15, and —CH2OR15;
• each of R16 and R17 is independently selected from:
• (a) H;
• (b) C3-7 cycloalkyl;
• (c) C1-4 alkyl;
• (d) C1-4 alkyl substituted with one or more C1-4 alkoxy, halogen, hydroxy, —COOR21, amino, mono(C1-4 alkyl)amino, di(C1-4 alkyl)amino or C6-10 aryl, wherein aryl is optionally substituted with one or more groups selected from halogen, C1-4 alkyl, hydroxy, amino, mono(C1-4 alkyl)amino, di(C1-4 alkyl)amino, and R15OOC—C1-4 alkyl-;
• (e) C6-10 aryl;
• and,
• (f) C6-10 aryl substituted with one or more halogen, hydroxy, amino, mono(C1-4 alkyl)amino, di(C1-4 alkyl)amino, and C1-4 alkyl;
• R22 and R23 independently represent H, C1-6 alkanoyl, C1-6 alkoxy-C1-6 alkanoyl-, aroyl, carbamoyl, and mono- or di-C1-6 alkylcarbamoyl;
• R15 is selected from H, C1-4 alkyl, C6-10 aryl, and C6-10 aryl-C1-4 alkyl-;
• and
• R21 is independently selected from hydrogen C1-4 alkyl, C6-10 aryl, and C6-10 aryl-C1-4 alkyl-;
• or a pharmaceutically acceptable salt thereof.